Can Remyelination Reverse Disability?

How can disability from multiple sclerosis be reversed?  An exciting approach is remyelination,  a process in which new myelin is made.   The myelin coating on nerve cells allows messages to travel rapidly such as from the brain down the spinal cord.  Loss of the myelin coating can delay or block the messages getting to where they need to go.  Chronic myelin loss may actually cause some nerve cells to slowly die. 

Myelin is formed from cells called oligos (short for oligodendrocytes) that wrap around and around multiple nerve cells.  In MS, the immune system attacks myelin, causing temporary or permanent myelin loss.

In the human brain, 5-8% of cells have the potential to grow-up to be myelin-making oligos.   These immature cells are called OPCs (oligodendrocyte precursor cells).   So how do we get these OPCs to create new myelin and repair old damage?  

One step is trying to make more of these OPC s.   Growth factors, such as PDGF-AA, can stimulate the OPCs to divide and multiply.   Another approach is attracting the potential myelin-making cells into the MS plaques.  Semaphorin- 3F, for example, is a protein that can attract OPCs to areas of loss of myelin. Chemokines are other compounds that can help OPCs to move into a plaque for remyelination.

Removing factors that block remyelination is a another way to try to repair myelin.   High levels of LINGO-1 , for example, prevent OPCs from maturing and making myelin.  An antibody to LINGO-1 allowed for remyelination to occur in animal models and is now being tested in human clinical trials.   Other antibody therapies are being developed that stimulate remyelination in animal models .  Whether these strategies will be effective and/or safe remains to be determined.

Research has led the way to effective treatments that reduce the immune attack against the brain, spinal cord and optic nerves.  However, multiple sclerosis still causes increasing disability for too many people.  While a cure is paramount, myelin-repair strategies will be an important frontier over this decade in the attempt to restore function.